阿昔洛韦与 HIV-1 感染者和 HSV-2 感染者之间 HIV-1 的传播。

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

机构信息

Department of Global Health, University of Washington, Harborview Medical Center, 325 Ninth Ave., Box 359927, Seattle, WA 98104, USA.

出版信息

N Engl J Med. 2010 Feb 4;362(5):427-39. doi: 10.1056/NEJMoa0904849. Epub 2010 Jan 20.

DOI:10.1056/NEJMoa0904849

PMID:20089951

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2838503/

Abstract

BACKGROUND

Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1.

METHODS

We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses.

RESULTS

A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed.

CONCLUSIONS

Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

摘要

背景

大多数感染人类免疫缺陷病毒 1 型（HIV-1）的人也同时感染单纯疱疹病毒 2 型（HSV-2），HSV-2 经常被重新激活，并与 HIV-1 的血浆和生殖器水平升高有关。抑制 HSV-2 的治疗可降低 HSV-2 再激活的频率以及 HIV-1 水平，这表明抑制 HSV-2 可能会降低 HIV-1 的传播风险。

方法

我们对仅一方伴侣 HIV-1 血清阳性（CD4 计数≥250 个细胞/立方毫米）且该伴侣同时感染 HSV-2 且在入组时未接受抗逆转录病毒治疗的夫妇进行了抑制性 HSV-2 治疗（阿昔洛韦，剂量为 400 mg 口服，每日两次）的随机、安慰剂对照试验。主要终点是未最初感染 HIV-1 的伴侣感染 HIV-1 的情况；通过病毒序列分析评估传播的关联性。

结果

共有 14 个非洲地点的 3408 对夫妇入组。在感染 HIV-1 的伴侣中，68%为女性，基线中位数 CD4 计数为 462 个细胞/立方毫米。在随机分组后发生的 132 例 HIV-1 血清学转换中（每 100 人年发病率为 2.7 例），132 例中有 84 例在夫妇内通过病毒序列关联在一起：阿昔洛韦组 41 例，安慰剂组 43 例（阿昔洛韦组的风险比为 0.92，95%置信区间为 0.60 至 1.41；P=0.69）。阿昔洛韦的抑制作用使 HIV-1 的平均血浆浓度降低了 0.25 log(10) 拷贝/毫升（95%置信区间为 0.22 至 0.29；P<0.001），HSV-2 阳性生殖器溃疡的发生率降低了 73%（风险比为 0.27；95%置信区间为 0.20 至 0.36；P<0.001）。92%的感染 HIV-1 的伴侣和 84%的未感染 HIV-1 的伴侣在研究中坚持 24 个月。研究药物的用药依从性为 96%。未观察到与阿昔洛韦相关的严重不良事件。